Published online Mar 14, 2021. doi: 10.3748/wjg.v27.i10.976
Peer-review started: November 23, 2020
First decision: January 7, 2021
Revised: January 12, 2021
Accepted: February 26, 2021
Article in press: February 26, 2021
Published online: March 14, 2021
Processing time: 107 Days and 17.5 Hours
Somatostatin analogues are an established first-line therapy for well differentiated small bowel neuroendocrine tumours (Wd-SBNETs), while and peptide receptor radionuclide therapy (PRRT) is frequently used as a second-line therapy. Adequate treatment selection of third-line treatment remains challenging due to the limited prospective data currently available on the best therapeutic sequence.
To understand current practice and rationale for decision-making by physicians in the 3rd-line setting by building an online survey.
Weighted average (WA) of likelihood of usage between responders (1 very unlikely; 4 very likely) was used to reflect the relevance of factors explored.
Replies from representatives of 28 centers were received (5/8/2020-21/9/2020); medical oncologist (53.6%), gastroenterologist (17.9%); United Kingdom (21.4%), Spain (17.9%), Italy (14.3%). Majority from European Neuroendocrine Tumor Society (ENETS) Centres of Excellence (57.1%), who followed ENETS guidelines (82.1%). Generally speaking, 3rd-line treatment for Wd-SBNETs was: everolimus (EVE) (66.7%), PRRT (18.5%), liver embolization (LE) (7.4%) and interferon-alpha (IFN) (3.7%); chemotherapy (0%); decision was based on clinical trial data (59.3%), or personal experience (22.2%). EVE was most likely used if Ki-67 < 10% (WA 3.27/4) or age < 70 years (WA 3.23/4), in the 3rd-line setting (WA 3.23/4); regardless of presence/absence of carcinoid syndrome (CS), rate of progression or extent of disease. Chemotherapy was mainly utilised only if rapid progression (within 6 mo) (WA 3.35/4), Ki-67 10%-20% (WA 2.77/4), negative somatostatin receptor imaging (WA 2.65/4) or high tumour burden (WA 2.77/4); temozolomide or streptozocin was used with capecitabine or 5-fluorouracil (5-FU) (57.7%), FOLFOX (5-FU combined with oxaliplatin) (23.1%). LE was selected if presence of CS (WA 3.24/4) or Ki-67 < 10% (WA 2.8/4), after progression to other treatments (WA 2.8/4). IFN was rarely used (WA 1.3/4).
Everolimus was the most frequently used therapeutic option in the third-line setting. The most important factors for decision-making included Ki-67, rate of progression, functionality and tumour burden; since this decision is based on multiple factors, it highlights the need for a multidisciplinary assessment.
Core Tip: Our survey delineates a possible treatment algorithm in patients with advanced small bowel neuroendocrine tumour (SBNET). While somatostatin analogues (SSAs), peptide receptor radionuclide therapy (PRRT) and everolimus are usually considered preferred first, second and third-line options respectively, chemotherapy is generally used when all other available treatments have failed. Locoregional therapies appear particularly useful when facing patients with functioning tumours, but their use is mainly limited to after at least two prior lines of treatment. We were also able to identify relevant unanswered questions in the field of advanced SBNET treatment, mainly in regards to the role of maintenance SSA after PRRT for non-functioning tumours. Multiple factors were identified as relevant at time of decision making; among them, Ki-67, rate of progression, tumour functionality and tumour burden may have a key role in helping physicians tailoring the treatment. Based on this, we would encourage for treatment decisions to be made within a multidisciplinary setting.